Non-infectious sarcoid-like inflammatory granulomatous conditions (NSIGC) associated with immune checkpoint inhibitors (ICIs) for cancer: Results from the International ICARUS (Immune Checkpoint Associated Rare and Unique Side effects) consortium.

12047 Background: ICIs can be associated with a broad range of toxicities; however, limited data exists on NSIGC secondary to ICIs. Herein, we assembled the first international cohort of patients (pts) with cancer who received ICIs and subsequently developed NSIGC. Methods: We retrospectively collected data from 14 institutions globally on pts with cancer who received ICIs between 2015-2025 and subsequently developed biopsy-confirmed NSIGC. Pts were eligible if they received anti-programmed cell death protein-1/programmed death-ligand 1 (anti-PD-1/PD-L1) alone or in combination with additional anti-cancer therapies such as chemotherapy, targeted agents or anti-CTLA-4, or if they were treated with other immunotherapies. The chi-squared goodness of fit test was used to analyze the distribution of different ICI regimens and their association with NSIGC, assuming a uniform distribution with an expected frequency of 25 for each of the 5 ICI regimens. Results: The study included 125 pts with biopsy-confirmed NSIGC post-ICI. Of these, 58.4% (n = 73) were male and 83.2% (n = 104) were Caucasians. Median age at cancer diagnosis was 62 years. The top three cancers in the cohort were melanoma (45.6%; n = 57), non-small cell lung cancer (16.8%; n = 21), and renal cell carcinoma (6.4%; n = 8). Out of 125 pts, 48.8% (n = 61) received anti-PD-1/PD-L1 monotherapy, 20% (n = 25) anti-PD-1/PD-L1 + anti-CTLA-4, 17.6% (n = 22) anti-PD-1/PD-L1 + chemotherapy, 8% (n = 10) anti-PD-1/PD-L1 + targeted agents, and 5.6% (n = 7) received other immunotherapies. Our result showed a significant difference between expected and observed NSIGC frequencies across different ICI regimens (X2 = 74.2, df = 4, p < 0.01), indicating a potential association between anti-PD-1/PD-L1 monotherapy and NSIGC. The median time to the diagnosis of NSIGC after ICI initiation was 7.1 months (range: 3.9-26.7 months). Of 125 pts, 55.2% (n = 69) were diagnosed after treatment completion. Among these 69 pts, 56.5% (n = 39) were diagnosed within 6 months, 14.5% (n = 10) between 6 months and 1 year, 10.1% (n = 7) between 1 and 2 years, and 18.8% (n = 13) were diagnosed after 2 years. The remaining 44.8% (n = 56) were diagnosed during treatment, out of which 48.2% (n = 27) required permanent treatment discontinuation due to NSIGC and 3.6% (n = 2) were re-challenged. 19.2% (n = 24) received steroid treatment for NSIGC. Conclusions: To our knowledge, this is the largest dataset to date demonstrating NSIGC as a rare side effect of ICIs. NSIGC frequently occurs after ICI therapy completion but can also result in ICI discontinuation. Biopsy confirmation is critical to prevent misdiagnosis, and further research is required to elucidate the biology, risk factors, and implications for ICI continuation or rechallenge to optimize patient outcomes.